Benzenemethanol, 2-[(3S)-3-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-hydroxypropyl]-.alpha.,.alpha.-dimethyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 29 to May 19, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted according to OECD and in accordance with GLP. The study material is well characterize

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

July 1992

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes

Remarks:

OECD Principles of Good Laboratory Practice, Statutory Instrument No. 654, 1997, ISBN 0-11-064105-1

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

(1S)-1-[3-[(1E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propanol

EC Number:

608-251-3

Cas Number:

287930-77-2

Molecular formula:

C29H28NO2Cl

IUPAC Name:

(1S)-1-[3-[(1E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propanol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

White powder, stored in dark at ambient temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK., Margate, Kent, England
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 175 - 232g
- Fasting period before study: overnight
- Housing: The dose range-finding animal was housed singly in a cage with dimensions 42 x 27 x 20 cm, and the main study animals were housed 5 per cage per sex with dimensions 59 x 38.5 x 20 cm
- Diet: Rat and Mouse No. 1 Maintenance Diet, supplied by Special Diets Services Limited, 1 Stepfield, Witham, Essex, CMS 3AD was available ad libitum throughout the study except for a period of food deprivation overnight prior to dosing until as soon as practicable after dosing.
- Water: Domestic mains quality water was available ad libitum throughout the study
- Acclimation period: 5 days before commencement of study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): During the study, mean environmental maximum and minimum temperatures were 22°c and 19°C
- Mean Humidity (%): 50 %
- Air changes (per hr): 15 minimum
- Photoperiod (hrs dark / hrs light):12/24

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

The available toxicity data suggested that an initial dose level of 2000 mg/kg would be suitable. The main study dose level was selected based on the results from the dose range-finding study.

The test material was administered orally in a single dose by means of a gavage at a constant dose volume of 10 ml/kg.
The dose was calculated based on the weight of the animal on the day of dosing.

Doses:

dose level: 2000 mg/kg

No. of animals per sex per dose:

A preliminary dose range-finding, using one female, at 2000 mg/kg indicated that this dose level would be suitable for the main study. 5 females and 5 males were used for this main study.

Control animals:

no

Details on study design:

The dose was calculated based on the weight of the animal on the day of dosing.

Formulations were administered within approximately 1 hour of preparation and were magnetically stirred during dosing.
All the animals were checked for viability early in the morning and again as late as possible on each day until sacrifice on Day 8 (dose range-finding) or Day 15 (main study).

Statistics:

No formal statistical analysis was conducted

Results and discussion

Preliminary study:

The available toxicity data suggested that an initial dose level of 2000 mg/kg would be suitable. The main study dose level was selected based on the results from the dose range-finding study.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no premature decedents during the study

Clinical signs:

other: Clinical signs were noted from approximately 5 to 6 hours after dosing and on Day 2. These signs were limited to wet, stained perigenital area and soft jelly­ like faeces

Gross pathology:

There were no abnormalities detected at necropsy.

Dose Level
(mg/kg) Animal/Sex Necropsy Finding Day of Death
2000 6-10male No abnormalities detected 15
11-15 female No abnormalities detected 15

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study following a single oral administration of L-744,341 to Sprague-Dawley rats, no mortality and no toxicity occurred at 2000 mg/kg

Executive summary:

There were no premature decedents or major clinical signs noted during the obsevation period.

Body weight performance was considered to be satisfactory, and there were no abnormalities detected at necropsy.

Under the conditions of the study following a single oral administration of L-744,341 to Sprague-Dawley rats, no mortality and no toxicity occurred at 2000 mg/kg